-
Toxicon : Official Journal of the... Jun 2024Mushroom poisonings are common in the United States. Gyromitrin (acetaldehyde N-methyl-N-formylhydrazone) is a clinically significant mycotoxin primarily associated with...
Mushroom poisonings are common in the United States. Gyromitrin (acetaldehyde N-methyl-N-formylhydrazone) is a clinically significant mycotoxin primarily associated with the lorchel (i.e. the false morel) Gyromitra esculenta. Resemblance between 'true and false morels' has resulted in misidentification of Gyromitra spp. as edible and sought after Morchella spp., resulting in toxicity. Despite literature evidence outlining toxic sequalae, Gyromitra spp. mushrooms are commonly consumed and prepared for culinary purposes. Classic clinical teachings emphasize significant neurotoxicity, including seizures, associated with ingestion of gyromitrin-containing mushrooms, stemming from gyromitrin's terminal metabolite monomethylhydrazine. We performed a longitudinal descriptive review of the clinical toxicity associated with ingestion of mushroom species known or suspected to contain gyromitrin in cases reported to the Michigan Poison & Drug Information Center between January 1, 2002, to December 31, 2020. Our 19-year descriptive case series of gyromitrin-containing mushroom ingestions reported to our Center demonstrated a preponderance of gastrointestinal signs and symptoms, including hepatotoxicity. Of 118 identified cases, 108 (91.5%) of the reported ingestions involved Gyromitra esculenta. The most frequent clinical findings associated with symptomatic ingestions (n= 83) were the aforementioned gastrointestinal symptoms (n=62; 74.7%). Neurological symptoms were less frequent (n=22, 26.5%) while hepatotoxicity occurred in fewer patients (n=14; 16.9%). Of symptomatic patients, most were treated with symptomatic and supportive care (n=58; 70%). Pyridoxine was used in a total of seven patients (n=7; 8.4%) with either hepatotoxicity or neurotoxicity. Medical outcomes ranged from minor to major, with no reported deaths. Patient presentations (i.e. GI vs. neurotoxic symptoms) following ingestion of gyromitrin-containing mushrooms may be highly variable and multifactorial, owing to differences in dose ingested, geographical distribution, genetic variability of both patient and mushroom species, and species-specific differences in toxin composition. Future research warrants species-level identification of ingested gyromitrin-containing mushrooms and investigating the contribution of genetic polymorphisms to differences in clinical toxidromes.
PubMed: 38908526
DOI: 10.1016/j.toxicon.2024.107825 -
Clinical Toxicology (Philadelphia, Pa.) May 2024Exposures to hydrazines occur during aeronautic and space operations and pose a potential risk to personnel. Historically, extensive preparatory countermeasures have...
INTRODUCTION
Exposures to hydrazines occur during aeronautic and space operations and pose a potential risk to personnel. Historically, extensive preparatory countermeasures have been taken due to concern for severe toxicity. This study seeks to better understand manifestations of acute occupational exposures to hydrazine to guide recommendations for management.
MATERIALS AND METHODS
A retrospective database review of records from four United States regional poison centers was conducted of all human exposures to hydrazine, monomethylhydrazine, or 1,1-dimethylhydrazine over two decades. Following case abstraction, descriptive statistics were performed to characterize demographics, manifestations, treatments, and outcomes.
RESULTS
One hundred and thirty-five cases were identified, and most were adult males exposed to inhaled hydrazine propellant vapors. Fifty-seven percent of patients were asymptomatic following exposure; otherwise, common symptoms were dyspnea, throat irritation, cough, ocular irritation, and headache. All patients were evacuated or received decontamination, with a few reports of symptomatic treatments, including oxygen supplementation and salbutamol (albuterol). Patients usually recovered quickly and were released after a brief healthcare facility evaluation or observed locally. No patients developed delayed symptoms. Symptoms of severe toxicity were not observed, and there were no deaths.
DISCUSSION
Acute exposures to hydrazines during operations within the aerospace industry appear to be limited primarily to mucosal and mild pulmonary irritation without significant neurologic, hepatic, or hematologic toxicity. These findings are contrary to previously established expectations and may be related to low-level exposures or possibly due to current emergency countermeasures.
CONCLUSIONS
Care in occupational hydrazine exposure will focus on evacuation, decontamination, and symptomatic management of chemical irritant properties of hydrazines. It is reasonable to manage mild cases outside of a healthcare facility. Continued endeavors in human space exploration and habitation will increase the risk of these exposures, making it imperative that clinicians be comfortable with the care and management of these patients.
Topics: Humans; Poison Control Centers; Male; Hydrazines; Retrospective Studies; Adult; United States; Female; Occupational Exposure; Middle Aged; Young Adult; Aged; Adolescent
PubMed: 38813683
DOI: 10.1080/15563650.2024.2350601 -
ENeurologicalSci Jun 2024A case-control study of sporadic amyotrophic lateral sclerosis (ALS) in a mountainous village in the French Alps discovered an association of cases with a history of...
A case-control study of sporadic amyotrophic lateral sclerosis (ALS) in a mountainous village in the French Alps discovered an association of cases with a history of eating wild fungi (false morels) collected locally and initially identified and erroneously reported as . Specialist re-examination of dried specimens of the ALS-associated fungi demonstrated they were members of the group, namely , species that have been reported to contain substantially higher concentrations of gyromitrin than present in . Gyromitrin is metabolized to monomethylhydrazine, which is responsible not only for the acute oral toxic and neurotoxic properties of false morels but also has genotoxic potential with proposed mechanistic relevance to the etiology of neurodegenerative disease. Most ALS patients had a slow- or intermediate-acetylator phenotype predicted by - () genotyping, which would increase the risk for neurotoxic and genotoxic effects of gyromitrin metabolites.
PubMed: 38770222
DOI: 10.1016/j.ensci.2024.100502 -
Aerospace Medicine and Human Performance Jul 2023Inhalation of hydrazine or hydrazine-derivative (for example, monomethylhydrazine) vapors during spaceflight operations remains a risk to crew and ground support... (Review)
Review
Inhalation of hydrazine or hydrazine-derivative (for example, monomethylhydrazine) vapors during spaceflight operations remains a risk to crew and ground support personnel. Here we sought to provide an evidence-based approach to inform acute clinical treatment guidelines for inhalational exposures during a noncatastrophic contingency spaceflight recovery scenario. A review of published literature was conducted concerning hydrazine/hydrazine-derivative exposure and clinical sequelae. Priority was given to studies that described inhalation though studies of alternative routes of exposure were additionally reviewed. Where possible, human clinical presentations were prioritized over animal studies. Rare human case reports of inhalational exposure and multiple animal studies provide evidence of varied clinical sequelae, including mucosal irritation, respiratory concerns, neurotoxicity, hepatotoxicity, hemotoxicity (including Heinz body development and methemoglobinemia), and longitudinal risks. In an acute timeframe (minutes to hours), clinical sequelae are likely to be limited to mucosal and respiratory risk; neurological, hepatotoxic, and hemotoxic sequelae are unlikely without recurrent, longitudinal, or noninhalational exposure. Acute clinical management should focus on likely clinical concerns as supported by existing data; recovery medical personnel should be prepared to manage mucosal irritation and respiratory concerns, including the potential need for advanced airway management. There is little evidence supporting the need for acute interventions for neurotoxicity and there is no evidence that acute hemotoxic sequelae would drive the need for on-scene management of methemoglobinemia, Heinz body development, or hemolytic anemia. Training that overemphasizes neurotoxic or hemotoxic sequelae or specific treatments for such conditions potentially raises the risk for inappropriate treatment or operational fixation.
Topics: Animals; Humans; Methemoglobinemia; Space Flight; Hydrazines
PubMed: 37349930
DOI: 10.3357/AMHP.6206.2023 -
Heliyon Mar 2023N- Nitrosodimethyl amine, the simplest member of the N-Nitrosamine family, is a carcinogenic and mutagenic agent that has gained considerable research interest owing to...
N- Nitrosodimethyl amine, the simplest member of the N-Nitrosamine family, is a carcinogenic and mutagenic agent that has gained considerable research interest owing to its toxic nature. Ozonation of industrially important hydrazines, such as unsymmetrical dimethylhydrazine (UDMH) or monomethylhydrazine (MMH), has been associated with NDMA formation and accumulation in the environment. UDMH/MMH - ozonation also leads to several other transformation products such as acetaldehyde dimethyl hydrazine (ADMH), tetramethyl tetra azene (TMT), diazomethane, methyl diazene, etc, which can be either precursors or competitors for NDMA formation. However, the relevant chemistry detailing the formation of these transformation products from UDMH/MMH -ozone reaction and their subsequent conversion to NDMA is not well understood. In this work, we explored the formation mechanism of ADMH and TMT from UDMH-ozonation and their further oxidation to NDMA using the second-order Moller Plesset perturbation theory employing the 6-311G(d) basis set. We have also investigated how MMH selectively forms methyl diazene and diazomethane under normal conditions and NDMA in the presence of excess ozone. Our calculations indicate that the reactions proceed via an initial H abstraction from the hydrazine -NH group, followed by the oxidation of the generated N-radical species. The formation of ADMH from the UDMH-ozone reaction involves an acetaldehyde intermediate, which then reacts with a second UDMH molecule to generate ADMH. The preferable attack of ozone molecule on N=C bond of ADMH generates DMAN intermediate, which subsequently undergoes oxidation to form NDMA. Unlike other transformation products, TMT formation occurs via the dimerization of DMAN. Though there exists an N=N bond in the TMT, which are preferable attacking sites for ozone, experimental studies show the lower yields of NDMA formation, which corroborates with the high activation barrier required for the process (42 kcal/mol). Overall, our calculated results agree well with the experimental observations and rate constants. Computational calculations bring new insights into the electronic nature and kinetics of the elementary reactions of this pathway, enabled by computed energies of structures that are not possible to access experimentally.
PubMed: 36967895
DOI: 10.1016/j.heliyon.2023.e14511 -
Frontiers in Neuroscience 2023The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former... (Review)
Review
The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former high-incidence foci of Western Pacific ALS and a hotspot of sALS in the French Alps. In both instances, there is a strong association with exposure to DNA-damaging (genotoxic) chemicals years or decades prior to clinical onset of motor neuron disease. In light of this recent understanding, we discuss published geographic clusters of ALS, conjugal cases, single-affected twins, and young-onset cases in relation to their demographic, geographic and environmental associations but also whether, in theory, there was the possibility of exposure to genotoxic chemicals of natural or synthetic origin. Special opportunities to test for such exposures in sALS exist in southeast France, northwest Italy, Finland, the U.S. East North Central States, and in the U.S. Air Force and Space Force. Given the degree and timing of exposure to an environmental trigger of ALS may be related to the age at which the disease is expressed, research should focus on the lifetime exposome (from conception to clinical onset) of young sALS cases. Multidisciplinary research of this type may lead to the identification of ALS causation, mechanism, and primary prevention, as well as to early detection of impending ALS and pre-clinical treatment to slow development of this fatal neurological disease.
PubMed: 36860617
DOI: 10.3389/fnins.2023.1005096 -
The Journal of Organic Chemistry Jul 2022A simple, efficient and highly regioselective method for the preparation of 3,4- and 4,5-disubstituted -methylpyrazoles in a one-pot procedure is reported. The...
A simple, efficient and highly regioselective method for the preparation of 3,4- and 4,5-disubstituted -methylpyrazoles in a one-pot procedure is reported. The methodology developed was based on the regiochemical control of the reaction of 4-acyl-1-pyrrole-2,3-diones and methylhydrazine with an influence of the addition or absence of acid and the substrate structure.
Topics: Monomethylhydrazine; Pyrroles
PubMed: 35687873
DOI: 10.1021/acs.joc.2c00657 -
Dalton Transactions (Cambridge, England... Nov 2021The great interest in aluminium nitride thin films has been attributed to their excellent dielectric, thermal and mechanical properties. Here we present the results of...
The great interest in aluminium nitride thin films has been attributed to their excellent dielectric, thermal and mechanical properties. Here we present the results of amorphous AlN films obtained by atomic layer deposition. We used trimethylaluminum and monomethylhydrazine as the precursors at a deposition temperature of 375-475 °C. The structural and mechanical properties and chemical composition of the synthesized films were investigated in detail by X-ray diffraction, X-ray photoelectron spectroscopy, electron and probe microscopy and nanoindentation. The obtained films were compact and continuous, exhibiting amorphous nature with homogeneous in-depth composition, at an oxygen content of as low as 4 at%. The mechanical properties were comparable to those of AlN films produced by other techniques.
PubMed: 34610072
DOI: 10.1039/d1dt02529e